JP6795585B2 - Axlインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法 - Google Patents
Axlインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法 Download PDFInfo
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020105211A (ja) * | 2015-05-29 | 2020-07-09 | ベルゲンビオ エイエスエイBerGenBio ASA | Axlインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法 |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6885390B2 (ja) * | 2016-02-26 | 2021-06-16 | 小野薬品工業株式会社 | Axl阻害剤と免疫チェックポイント阻害剤とを組み合わせて投与することを特徴とする癌治療のための医薬 |
| US10639368B2 (en) | 2016-05-27 | 2020-05-05 | Agenus Inc. | Anti-TIM-3 antibodies and methods of use thereof |
| IL265800B2 (en) | 2016-10-11 | 2023-10-01 | Agenus Inc | Anti-LAG-3 antibodies and methods of using them |
| US11576873B2 (en) | 2017-03-31 | 2023-02-14 | The Curators Of The University Of Missouri | Compositions for the treatment of drug-resistant tumors and methods of use thereof |
| WO2019039525A1 (ja) * | 2017-08-23 | 2019-02-28 | 小野薬品工業株式会社 | Axl阻害剤を有効成分として含むがん治療剤 |
| WO2019074116A1 (ja) | 2017-10-13 | 2019-04-18 | 小野薬品工業株式会社 | Axl阻害剤を有効成分として含む固形がん治療剤 |
| BR112020026641A2 (pt) * | 2018-06-27 | 2021-03-30 | Oscotec Inc. | Derivados de piridopirimidinona para o uso como inibidores de axl |
| UY38349A (es) | 2018-08-30 | 2020-03-31 | Array Biopharma Inc | Compuestos de pirazolo[3,4-b]piridina como inhibidores de cinasas tam y met |
| GB201912059D0 (en) | 2019-08-22 | 2019-10-09 | Bergenbio As | Combaination therapy of a patient subgroup |
| GB202004189D0 (en) | 2020-03-23 | 2020-05-06 | Bergenbio As | Combination therapy |
| GB202006072D0 (en) * | 2020-04-24 | 2020-06-10 | Bergenbio Asa | Method of selecting patients for treatment with cmbination therapy |
| GB202104037D0 (en) | 2021-03-23 | 2021-05-05 | Bergenbio Asa | Combination therapy |
| EP4359439A1 (en) | 2021-06-24 | 2024-05-01 | Yeda Research and Development Co. Ltd | Combination therapy for the treatment of cancer comprising an anti-egfr antibody and an axl-inhibitor |
| GB202209285D0 (en) | 2022-06-24 | 2022-08-10 | Bergenbio Asa | Dosage regimen for AXL inhibitor |
| AR129722A1 (es) | 2022-06-28 | 2024-09-18 | Arcus Biosciences Inc | Compuestos inhibidores de axl |
| KR20240156104A (ko) * | 2023-04-21 | 2024-10-29 | 아주대학교산학협력단 | 면역 관문 억제제 저항성 극복을 위한 암의 예방 또는 치료용 약학적 조성물 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2226211A1 (de) | 1972-05-30 | 1973-12-13 | Basf Ag | N-substituierte iminocumarinfarbstoffe |
| AU2905199A (en) * | 1999-03-15 | 2000-10-04 | Trustees Of The University Of Pennsylvania, The | Combined therapy with a chemotherapeutic agent and an oncolytic virus for killing tumor cells in a subject |
| US6149495A (en) | 1999-03-15 | 2000-11-21 | Austin; Joseph James | Confetti and theatrical snow delivery device |
| EP1382969A1 (en) | 2002-07-17 | 2004-01-21 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Diagnosis and prevention of cancer cell invasion |
| AU2003286746A1 (en) | 2002-10-29 | 2004-05-25 | Rigel Pharmaceuticals, Inc. | Modulators of angiogenesis and tumorigenesis |
| WO2007030680A2 (en) | 2005-09-07 | 2007-03-15 | Rigel Pharmaceuticals, Inc. | Triazole derivatives useful as axl inhibitors |
| CA2647282A1 (en) * | 2006-04-05 | 2007-10-11 | Pfizer Products Inc. | Ctla4 antibody combination therapy |
| AU2007307652A1 (en) | 2006-10-10 | 2008-04-17 | Squicor | Compositions and methods for treating and diagnosing cancers |
| US8097630B2 (en) | 2006-10-10 | 2012-01-17 | Rigel Pharmaceuticals, Inc. | Pinane-substituted pyrimidinediamine derivatives useful as Axl inhibitors |
| JP2008130120A (ja) | 2006-11-17 | 2008-06-05 | Sharp Corp | 光ピックアップ装置 |
| WO2008080134A2 (en) | 2006-12-22 | 2008-07-03 | Rigel Pharmaceuticals, Inc. | 4-amin0-2- (hetero) arylamino-5- (hetero) arylthiazoles useful as axl inhibitors |
| US9650391B2 (en) | 2006-12-29 | 2017-05-16 | Rigel Pharmaceuticals Inc. | N3-heteroaryl substituted triazoles and N5-heteroaryl substituted triazoles useful as Axl inhibitors |
| CA2710230C (en) | 2006-12-29 | 2016-02-23 | Rigel Pharmaceuticals, Inc. | Bridged bicyclic aryl and bridged bicyclic heteroaryl substituted triazoles useful as axl inhibitors |
| PL2078010T3 (pl) * | 2006-12-29 | 2014-07-31 | Rigel Pharmaceuticals Inc | Triazole podstawione policyklicznym heteroarylem użyteczne jako inhibitory Axl |
| ES2558477T3 (es) | 2006-12-29 | 2016-02-04 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos útiles como inhibidores de AXL |
| ES2406930T3 (es) | 2006-12-29 | 2013-06-10 | Rigel Pharmaceuticals, Inc. | Triazoles sustituidos con arilo bicíclico y heteroarilo bicíclico útiles como inhibidores de AXL |
| EP2102356A2 (en) | 2007-01-09 | 2009-09-23 | Brystol-Myers Squibb Company | Identification of polynucleotides for predicting activity of compounds that interact with and/or modulate protein tyrosine kinases and/or protein tyrosine kinase pathways in prostate cells |
| JP2010523712A (ja) * | 2007-04-13 | 2010-07-15 | スーパージェン, インコーポレイテッド | 癌または過剰増殖の治療に有用なaxlキナーゼ阻害剤 |
| EP2137535B1 (en) | 2007-04-13 | 2015-06-03 | Dana-Farber Cancer Institute, Inc. | Receptor tyrosine kinase profiling |
| SI2205592T1 (sl) | 2007-10-26 | 2013-09-30 | Rigel Pharmaceuticals, Inc. | Triazoli substituirani s policikličnim arilom in triazoli substituirani s policikličnim heteroarilom uporabni kot Axl inhibitorji |
| NZ599628A (en) | 2007-11-12 | 2013-11-29 | U3 Pharma Gmbh | Axl antibodies |
| PE20091024A1 (es) | 2007-11-15 | 2009-08-12 | Chugai Pharmaceutical Co Ltd | Anticuerpos monoclonales que se unen a anexelekto y sus usos |
| SI2851374T1 (sl) | 2007-12-14 | 2017-08-31 | Bristol-Myers Squibb Company | Vezavne molekule k humanemu ox40 receptorju |
| US8735064B2 (en) | 2007-12-24 | 2014-05-27 | Bergenbio As | Methods for creating and identifying functional RNA interference elements |
| US8546433B2 (en) * | 2009-01-16 | 2013-10-01 | Rigel Pharmaceuticals, Inc. | Axl inhibitors for use in combination therapy for preventing, treating or managing metastatic cancer |
| KR20120035145A (ko) | 2009-05-11 | 2012-04-13 | 우드라이 파마 게엠베하 | 인간화 axl 항체 |
| JP5669732B2 (ja) | 2009-05-15 | 2015-02-12 | 中外製薬株式会社 | 抗axl抗体 |
| AU2010303149B2 (en) * | 2009-09-30 | 2016-08-04 | Board Of Regents, The University Of Texas System | Combination immunotherapy for the treatment of cancer |
| US20130064831A1 (en) | 2010-05-17 | 2013-03-14 | Bristol-Myers Squibb Company | Immunotherapeutic dosing regimens and combinations thereof |
| BR112012027995A2 (pt) * | 2010-06-18 | 2017-01-10 | Genentech Inc | anticorpo e ácido nucleíco isolado, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica, uso do anticorpo, método de tratamento de um indivíduo com câncer, de um indivíduo possuíndo um distúrbio imune, de inibição da angiogênese e para inibir a ativação constitutiva de axl |
| NZ714128A (en) | 2010-09-09 | 2017-10-27 | Pfizer | 4-1bb binding molecules |
| KR20140104944A (ko) | 2011-06-22 | 2014-08-29 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 항-axl 항체 및 그의 용도 |
| EP2723377B1 (en) | 2011-06-22 | 2018-06-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-axl antibodies and uses thereof |
| WO2013180949A1 (en) * | 2012-05-27 | 2013-12-05 | Ning Xi | Substituted quinoline compounds and methods of use |
| NZ711946A (en) | 2013-03-14 | 2020-05-29 | Icahn School Med Mount Sinai | Newcastle disease viruses and uses thereof |
| TWI649308B (zh) * | 2013-07-24 | 2019-02-01 | 小野藥品工業股份有限公司 | 喹啉衍生物 |
| GB201410826D0 (en) * | 2014-06-18 | 2014-07-30 | Bergenbio As | Anti-axl antibodies |
| GB201410825D0 (en) * | 2014-06-18 | 2014-07-30 | Bergenbio As | Anti-axl antibodies |
| EP3226856A4 (en) | 2014-12-02 | 2018-07-11 | Celgene Corporation | Combination therapies |
| US10208121B2 (en) * | 2014-12-18 | 2019-02-19 | Bergen Teknologioverforing As | Anti-Axl antagonistic antibodies |
| GB201509338D0 (en) | 2015-05-29 | 2015-07-15 | Bergenbio As | Combination therapy |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020105211A (ja) * | 2015-05-29 | 2020-07-09 | ベルゲンビオ エイエスエイBerGenBio ASA | Axlインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法 |
| JP2022141811A (ja) * | 2015-05-29 | 2022-09-29 | ベルゲンビオ エイエスエイ | Axlインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法 |
| JP7229194B2 (ja) | 2015-05-29 | 2023-02-27 | ベルゲンビオ エイエスエイ | Axlインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法 |
| JP7549627B2 (ja) | 2015-05-29 | 2024-09-11 | ベルゲンビオ エイエスエイ | Axlインヒビタおよび免疫チェックポイントモジュレータまたは腫瘍溶解性ウィルスによる併用療法 |
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| GB201516442D0 (en) | 2015-10-28 |
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| JP7549627B2 (ja) | 2024-09-11 |
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| US20230149397A1 (en) | 2023-05-18 |
| EP3302481A1 (en) | 2018-04-11 |
| JP7229194B2 (ja) | 2023-02-27 |
| US20180153888A1 (en) | 2018-06-07 |
| JP2018521116A (ja) | 2018-08-02 |
| US11534440B2 (en) | 2022-12-27 |
| JP2022141811A (ja) | 2022-09-29 |
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